UCB backs epilepsy-focused digital heath startup Nile AI

Belgian drugmaker UCB has been steadily building its digital health expertise for several years, and that includes nurturing new projects. One of those is now being launched as a new company – Nile AI – that aims to improve the care of people with epilepsy.

UCB is bankrolling Los Angeles-based Nile with €25 million (around $29 million) in startup cash and will be a majority shareholder, with a presence on the company’s board as well as options on acquiring “data and insights” from its platform.

Nile is being formed to develop a digital health platform – consisting of a patient app that links to a portal for healthcare professionals – that can use data from patients’ past epileptic seizures to try to predict future attacks.

The patient app connects individuals with their care team, and provides information about their treatment and progress, while the portal shows the status of patients, maintains support between consultations, and allows data-driven decisions on treatment and care, according to UCB.

The digital tools are being piloted at Massachusetts General Hospital and Michigan State University Healthcare, and the aim is to have it ready for a commercial launch before the end of this year.

“We know that patients suffering from epilepsy struggle with the unpredictable nature of their lives,” said Dr Leo Petrossian, Nile AI’s CEO.

“Every single day they awake uncertain of what they can expect. At Nile, we believe that all of the data to predict the path of an epilepsy patient exists, though it is fragmented and disconnected.”

Nile’s software operates as a care management system, and cam be used to address this uncertainty, he continued, with the ultimate goal of shortening the time it takes for people with epilepsy to be on the best care available.

It’s a mission that dovetails with UCB’s position as a well-established player in the epilepsy category. Medicines like Vimpat (lacosamide), Keppra (levetiracetam), Briviact (brivaracetam) and recent launch Nayzilam (midazolam) nasal spray collectively make upwards of €2.3 billion a year and account for almost half of its net sales.

UCB added to its range last June with the $270 million acquisition of Engage Therapeutics and its Staccato Alprazolam product for the rapid termination of seizures.

“UCB has a deep understanding of epilepsy and the challenges that people living with the disease face every day, including how patients communicate with their healthcare providers,” said the Belgian firm’s head of neurology Charl Van Zyl.

“We think Nile’s platform can provide valuable insights and foster a better care management experience for people living with epilepsy.”

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Could Lilly’s donanemab readout in Alzheimer’s boost Biogen’s prospects?

When Eli Lilly reported results for donanemab in Alzheimer’s disease earlier this week it was hailed as a rare win for the amyloid hypothesis, although there’s no shortage of candidates that have failed despite positive mid-stage trial results.

Some analysts have intimated that given the small size of the study at just over 270 patients, rival amyloid drug developers Biogen and Eisai could claim the biggest benefit from the data in positive sentiment ahead of an FDA decision later this year.

Goldman Sachs analyst Terence Flynn said the result was a “positive surprise” after Lilly revealed top-line data from the TRAILBLAZER-ALZ study showing that donanemab slowed cognitive decline by a third in people with early Alzheimer’s and completely resolved the amyloid beta plaques that are a hallmark of the disease.

Flynn also said the data was an “incremental positive” for Biogen, whose Eisai-partnered aducanumab is already filed for approval and awaiting an FDA decision by 7 March, as it lends further weight to the amyloid beta hypothesis of Alzheimer’s.

Biogen is nearest to market with aducanumab but a positive verdict from the US regulator is far from assured. In November, an FDA advisory committee voted ten to one against approval, saying the clinical data backing the drug was inconclusive, but that came on the back of a positive assessment by the FDA’s own reviewer.

Wolfe analyst Tim Anderson said in a research note issued ahead of the donanemab readout that the FDA could be influenced by the donanemab data and – if positive – that would raise the chances of a greenlight for aducanumab.

There’s an alternative view however that donanemab’s data might actually harm aducanumab’s prospects. Analysts at Jefferies told Barron’s this week that the FDA may have been minded to approve Biogen and Eisai’s drug because there were no other late-stage candidates in play, but Lilly’s drug could change that perception.

Donanemab is unlike most other amyloid-targeting drugs – including aducanumab – because it targets a pyroglutamated form of amyloid beta called N3pG that is found only in amyloid plaques and according to some research can stimulate misfolding of proteins.

Lilly’s hypothesis – as yet unproven – is that clearing those plaques has a direct association with cognitive benefits.

Lilly says TRAILBLAZER-ALZ met its primary endpoint, slowing decline on the Integrated Alzheimer’s Disease Rating Scale in the donanemab group by 32% compared to placebo, with trends towards improvement on secondary endpoints that didn’t hit statistical significance.

On safety, around 27% of the treatment arm showed ARIA-E – an inflammatory reactions also seen with other amyloid-targeting antibodies – but there’s little other data available yet.

Lilly started a 500-patient phase 2 trial called TRAILBLAZER-ALZ-2 last June that it suggests could serve as a confirmatory pivotal study and potentially support regulatory filings – dramatically shortening the development timeline for the drug. That’s due to read out in next year or later.

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RNAi biotech Atalanta debuts with $110m plus Biogen and Roche CNS tie-ups

US biotech Atalanta Therapeutics has come out of stealth mode backed with $110m from Biogen and Roche, who have also signed separate partnerships to develop new therapies for neurological diseases using RNA interference (RNAi) technology.

While there are RNAi products on the marketplace, with Alnylam becoming the first company to get a product approved in 2018, it is difficult to get this class of drug distributed through the brain and spinal cord.

But with new technology based on branched silencing RNA licensed from the University of Massachusetts Medical School, Atalanta says it could change this.

Co-founded by Craig Mello, who won the Nobel Prize for Physiology or Medicine in 2006 for his work on RNAi, the company says the technology could be used to treat central nervous system diseases such as Huntington’s, Alzheimer’s and Parkinson’s.

Atalanta has actually been working since 2018 with co-founders Anastasia Khvorova, a UMass biochemist and Neil Aronin, a professor from University of Massachusetts Medical School, providing early leadership.

The company hired Alicia Secor as CEO in summer of 2019, who has previously been CEO of Juniper Pharmaceuticals and serves on the boards of neurology and rare diseases firms GW Pharmaceuticals and Orchard Therapeutics.

Atalanta starts life with two different strategic collaborations with its big pharma backers.

The partnership with Biogen will develop RNAi therapeutics for multiple targets, including HTT for the treatment of Huntington’s disease, as well as additional unnamed CNS targets.

Atalanta will be eligible to receive development and milestone payments as well as undisclosed royalties on any resulting products.

The strategic collaboration with Genentech entails the development of RNAi therapeutics for multiple CNS targets for neurodegenerative diseases, including Parkinson’s disease and Alzheimer’s disease.

This could also result in development and milestone payments and royalties.

Unprecedented and astounding

In an interview with pharmaphorum Secor said that the technology comes from a discovery in Khvorova’s lab, which showed the technology allowed potent silencing of Huntington’s for six months in mice.

In 2019 results were published in Nature Biotechnology of the research findings, which were described by Secor as “unprecedented and astounding”.

The founders formed the company with backing from investor F-Prime Capital and has just launched its Series A round with Roche’s Genentech unit and Biogen the first to invest.

Secor said: “In my 30 years I have never seen this level of interest.”

The technology could be used in several indications, according to chief scientific officer and RNAi expert Aimee Jackson.

“There is distribution to multiple regions and deep brain structures and enhanced potency and duration of action,” she said.

With the backing the company already has, Secor said the plan is to focus on preclinical development without needing to worry about funding for the time being.

Quizzed about the possibility of an IPO or buyout from a big pharma company, Secor said the focus is very much on developing the technology.

She told pharmaphorum: “Our long-term vision is to be discovery research and commercialisation platform and product company for a very long time.

“We have a long cash runway to do some building,” she added.

Female leadership

Secor also noted the strong role that women have played in founding and running the company, noting that the name Atalanta refers to the famous female character from Greek mythology.

It also reflects the contribution from Khorova as the founder of the company.

There’s also a connection with Greek mythology from the name of the protein that is targeted by the RNAi drug in Huntington’s – Argonaute 2.

In many versions of Jason’s quest for the Golden Fleece, Atalanta served as the only woman on the crew of the Argo.

Secor noted the recent appointments of Emma Walmsley and Reshma Kewalramani as CEOs at GlaxoSmithKline and Vertex, respectively.

She told pharmaphorum: “I wanted to keep the name to remind us we were named after a woman.

“I think there is a big movement around diversity and inclusion its an opportunity to break through those glass ceilings women should be feeling empowered to take leadership roles.

“It creates a whole lot of opportunities for women. This is a good time for women and I am excited to see more women step into leadership roles.”

 

 

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Neurology’s Growing Need for Disposable Technologies

By Boris Goldstein, Co-Founder & Executive Chairman at Brain Scientific COVID-19 is known for its impacts on a patient’s respiratory system, but it has also been found to affect individuals in unique ways and with varying severity levels depending on their age, risk factors, and comorbidities. Several studies have recently shown that the development of neurological conditions and symptoms are prevalent in COVID patients. Neurologic manifestations, including headaches, myalgias, dizziness, and encephalopathy, occur in most hospitalized COVID-19 patients. According to a recent study published in Annals of Clinical and Translational Neurology, 42% of these symptoms were present at the onset,

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Angelini and Arvelle create neurology player with $960m merger

There’s a new player in the neurology and mental health drugs market after Italy’s Angelini Pharma merged with Switzerland’s Arvelle Therapeutics in a deal worth up to $960 million based around the anti-seizure drug cenobamate.

Angelini is an international pharma company that is part of the privately-owned Italian Angelini Group, while Arvelle is focused on bringing innovative treatments to patients suffering from CNS disorders.

The deal gives Angelini an exclusive European license to market cenobamate, a drug being developed for drug-resistant focal-onset seizures in adults.

It is already in the late stages of development and expected to be approved in Europe later this year.

The license covers the European Union and other countries in the European Economic Area, such as Switzerland and the UK. As a result the all-cash deal will see Angelini pay $610 million following regulatory approval of cenobamate, followed by a further payment of $340 million.

Arvelle was founded in 2019 and has been focused on developing cenobamate, which has already been designated as a Promising Innovative Medicine by the UK regulator, the Medicines and Healthcare products Regulatory Agency (MHRA).

It is a small molecule with a dual action, which stimulates the γ-aminobutyric acid (GABAA) ion channel while also inhibiting voltage-gated sodium currents.

Study findings so far have shown cenobamate can produce a significantly greater reduction in median seizure frequency and more patients achieving a 50% or greater reduction in seizure frequency compared to the placebo group.

It is already approved by the FDA as an anti-seizure drug for partial-onset (focal onset) seizures in adults, where it is available under the brand name Xcopri and marketed by SK Biopharmaceuticals, which discovered and developed it.

SK Biopharmaceuticals, a pharmaceutical company listed on the Korea Stock Exchange, announced that it has agreed to sell its 12% stake in Arvelle Therapeutics to Angelini Pharma.

SK Biopharmaceuticals will remain eligible to receive all payments inherited by a license agreement signed between Arvelle Therapeutics and SK Biopharmaceuticals in February 2019.

Revenue share payments due to certain of the Arvelle shareholders will be assumed by Angelini Pharma.

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Clene goes public with gold-based neurology nanotechnology

Biotech Clene Nanomedicine has gone public with a mission to use nanotherapeutics that will use gold to treat devastating neurological diseases including Parkinson’s disease.

Over the Christmas period Clene closed a reverse merger with Tottenham Acquisition I Limited, allowing shares to be publicly traded on the Nasdaq stock exchange.

The US-based company says it aims to revolutionise treatment of diseases including multiple sclerosis and amyotrophic lateral sclerosis with a new class of drugs that use gold to catalyse the cellular reactions fundamental to life.

Proceeds from the transaction totalled $31.9 million, combining funds held in Tottenham’s trust account and financing from Clene shareholders.

The current pipeline includes a phase 3 study in ALS and four phase 2 studies in ALS, MS and Parkinson’s.

Lead candidate is CNM-Au8, is an orally administered, bioenergetic gold nanocatalyst designed to enhance critical intracellular bioenergetic reactions necessary for repairing and reversing neuronal damage.

The company says its approach is based on the understanding that energy is the essential building block to life and that bioenergetic failure underlies the makeup of many neurodegenerative diseases.

Clene says its technology is based on active nanocrystals to activate reactions within the body that have shown to enhance cellular repair and regeneration.

Preliminary blinded data from the phase 2 RESCUE-ALS trial announced at the Symposium on ALS/MND show that more than 40% of enrolled patients with completed 12-week data experienced an improvement in motor neuron function as assessed by a standardised score.

Compared to baseline values the average score showed an increase that exceeded the expectations on which the study was based, the company said.

This suggested that CNM-Au8 may have neuro-reparative potential in ALS and expects completed unblinded results from the RESCUE-ALS study in the second half of 2021.

CNM-Au8 was selected as one of the first drug regimens to be evaluated in the phase 3 HEALEY ALS Platform Trial, a placebo-controlled study testing several novel ALS therapies at the same time to cut costs.

It includes substantial financial support from philanthropic donors and foundations and provides access to 54 expert ALS clinical trial sites across the US.

Dosing was initiated in the Clene-specific portion of the platform trial in July 2020 and full enrolment is expected by the end of Q2 2021, with top-line data available in the first half of 2022.

 

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AI-designed serotonin tracker could help develop neurology drugs

A serotonin sensor designed using Artificial Intelligence (AI) could help scientists study sleep and mental health and potentially find new neurology drugs.

The US National Institutes of Health said that the research it had co-funded used AI to transform a bacterial protein into a new research tool.

It is hoped that the protein, which “catches” serotonin molecules and allows them to be tracked, could detect subtle, real-time changes in serotonin levels during sleep, fear and social interactions.

The technique could also be used to test the effectiveness of new psychoactive drugs, according to the US-government funded NIH.

This study in mice was funded by the NIH’s Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) initiative, which aims to revolutionise understanding of the brain under healthy and disease conditions.

It was led by researchers in the lab of Dr Lin Tian, principal investigator at the University of California Davis School of Medicine.

In the study, researchers transformed a nutrient-grabbing Venus-flytrap shaped bacterial protein into a highly sensitive fluorescent sensor that lights up when it captures serotonin.

Tian’s lab builds on the work of scientists in the lab of Dr Loren Looger, Howard Hughes Medical Institute Janelia Research Campus, Ashburn, Virginia, who used traditional genetic engineering techniques to convert the bacterial protein into a sensor of the neurotransmitter acetylcholine.

Tian worked with Looger’s team and used artificial intelligence to completely redesign the protein known as OpuBC to catch serotonin instead.

The researchers used machine learning algorithms to help a computer ‘think up’ 250,000 new designs. After three rounds of testing, the scientists settled on one.

Experiments in mouse brain slices showed the sensor responded to serotonin signals sent between neurons at synaptic communications points.

Further experiments on cells in petri dishes suggested that the sensor could effectively monitor changes in these signals caused by drugs, including cocaine, MDMA and several commonly used antidepressants.

Mouse studies showed the sensor monitored an expected rise in serotonin levels when mice were awake and a fall as mice fell asleep.

They also spotted a greater drop when the mice eventually entered the deeper, REM sleep states.

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Novartis buys neurology biotech Cadent for up to $770m

Novartis is to buy neuroscience drugs firm Cadent Therapeutics in a deal worth up to $770 million.

The big Swiss pharma already has a presence in neurology with its multiple sclerosis drug Gilenya (fingolimod) and the more recently approved Aimovig (erenumab).

With the acquisition of Cambridge, Massachusetts-based Cadent, Novartis gains rights to a portfolio of neurology drugs.

This includes CAD-9303, a NMDAr positive allosteric modulator that could be used to treat schizophrenia, and MIJ-821, a NMDAr negative allosteric modulator for depression that was licensed to Novartis in 2015.

MIJ-821 is already in phase 2 development for treatment-resistant depression in a trial overseen by Novartis and the acquisition includes a buyout of milestones payments and royalties for the drug.

Gopi Shanker, the interim co-head of neuroscience at the Novartis Institutes for BioMedical Research (NIBR), added: “There is good evidence, both from human genetics as well as clinical studies, that NMDA receptors, which regulate learning, memory and plasticity in the brain function sub-optimally in schizophrenia.

“By modulating the activity of these receptors, we think CAD-9303 could potentially treat negative and cognitive symptoms and help address one of the key gaps in schizophrenia care.”

Additionally, Novartis will gain full rights to CAD-1883, a clinical stage SK channel positive allosteric modulator in development for movement disorders.

Cadent, which launched in 2017 through the merger of Luc Therapeutics and Ataxion Therapeutics, will receive $210 million up front, and up to $560 million in milestone payments.

No other financial details were disclosed.

Cadent said that its pipeline of drugs could also be used to treat indications such as movement disorders.

The transaction has been approved by the board of directors and stockholders of Cadent Therapeutics. Cadent and Novartis expect the transaction will close during the first quarter of 2021.

Closing of the transaction is subject to customary closing conditions, including antitrust review under us antitrust laws.

Investors in Cadent include Atlas Venture, Cowen Healthcare Investments, Qiming Venture Partners, Access Industries, Clal Biotechnology Industries, Novartis Corporate and Slater Technology Fund.

 

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9th Annual Neurodegenerative Drug Development Summit

The 9th Neurodegenerative Drug Development Summit is the industry’s definitive and unrivalled forum focused on revealing hot and promising pockets of innovation in drug discovery for neurodegenerative diseases and combating translational challenges by shining a light on pioneering companies leading the way to meet this dire medical need.

Building on the success of last year’s meeting, this year’s program showcases new biotechs trailblazing this space and will put the spotlight on the latest scientific in diverse targetsnovel modalities and innovative trial design. Hear from our expert speakers from the likes of Sanofi, Alzheon, European Medicines Agency, Lundbeck and Alector.

Across 3 action-packed, case-study driven days and 2 parallel tracks of content, we present the opportunity to join us online in 2021 to overcome technical and operational challenges preventing you and your team from translating promising preclinical research into evidenced clinical benefit.

Whether you are working in a team dedicated to Parkinson’sAlzheimer’sALSFrontotemporal Dementia or a rare neurodegenerative disorder, join this intimate, industry-led forum to not only to learn from those spearheading this space, but to network and build meaningful partnerships with over 180 neurodegenerative drug development experts. After all, collaboration in this industry is pivotal.

Download the program here to learn more about the digital summit.

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Lilly pays up to $1.04bn for neurology gene therapy biotech Prevail

Eli Lilly has acquired Prevail, a biotech focusing on gene therapies for neurodegenerative diseases including Parkinson’s, in a deal potentially worth more than $1 billion.

The big US pharma is to pay up to $1.04 billion to buy Prevail, paying $22.5 per share up front plus a $4 contingent value right (CVR) to sweeten the deal.

The CVR pays out if one of Prevail’s gene therapies is approved in one of several developed countries before December 31, 2024.

Prevail is working on gene therapies based on adeno-associated virus 9 (AAV9) technology, which must be approved in any of the group of countries comprising the US, Japan, UK, Germany, France, Italy, or Spain.

Lilly pointed out that there can be no assurance of payouts from the CVR – something that shareholders in other companies have found out the hard way.

Sanofi last year settled with holders of a CVR dating back to the French pharma’s acquisition of Genzyme that was contingent on MS drug Lemtrada achieving several goals – cash that never materialised.

And former Celgene shareholders are currently sweating over a CVR relating to three cancer drugs that looks increasingly unlikely to pay out because of delays with FDA reviews.

The acquisition is set to close in the first quarter of 2021 and will see several gene therapies added to the company’s pipeline.

Top of the list is PR001, a potentially disease-modifying single-dose gene therapy for Parkinson’s disease with GBA1 mutations (PD-GBA) and the rare condition neuronopathic Gaucher disease (nGD) that is injected into a gap at the base of the brain stem.

The phase 1/2 PROPEL clinical trial in PD-GBA is ongoing and the phase 1/2 PROVIDE trial in nGD has been granted Fast Track Designation in these indications.

Also in the pipeline is PR006 for patients with frontotemporal dementia with GRN mutations (FTD-GRN), also delivered by an injection in the same place.

This is being tested in the phase 1/2 PROCLAIM trial, where the first patient was dosed earlier this month.

Prevail is also developing PR004 for neurodegenerative diseases associated by the abnormal accumulation of alpha-synuclein protein in neurons, nerve fibres or glial cells.

It is also working on therapies for Alzheimer’s and amyotrophic lateral sclerosis (ALS).

Lilly’s CEO David Ricks is pursuing a policy of “bolt-on” acquisitions to add to the company’s pipeline, and scooped up dermatology specialist Dermira in a similar-sized deal at the beginning of the year.

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Swiss start-up Noema raises $59m to develop neurology drugs offloaded by Roche

Swiss biotech Noema has raised 54 million Swiss francs ($59m) to develop four neurological disorder drugs licensed in from Roche.

The company is developing four phase 2 drugs brought in from Roche after the big Swiss pharma decided somebody else should take the risk of developing them.

Roche, which decided the products were surplus to requirements in an already-packed pipeline, also received a shareholding in Noema, in exchange for rights to the four clinical-stage product-candidates.

Lead product is NOE-101, an mGluR5 inhibitor that is ready for phase 2b trials in two indications – for persistent seizures in Tuberous Sclerosis Complex and severe pain in Trigeminal Neuralgia.

The company is also preparing NOE-15, a PDE10A inhibitor for phase 2b testing to treat Tourette Syndrome.

It also has two other clinical stage assets – mGluR2/3 inhibitor NOE-109 and NOE-115, a triple reuptake inhibitor that are being evaluated in undisclosed indications.

The latest financing round was co-led by Sofinnova Partners, a European life sciences venture capital firm based in Paris, London and Milan, and Polaris Partners, a healthcare and technology investment firm based in the US.

The global consortium of new international investors includes Gilde Healthcare, Invus and BioMed Partners.

Noema was founded last year with a seed investment from Sofinnova partners and is led by CEO Luigi Costa, former CEO of haematology and oncology firm Nordic Nanovector.

He was also a senior figure at Onyx Pharmaceuticals, which was acquired by Amgen in 2014 and led the company’s international organisation and the launch of multiple myeloma drug Kyprolis outside the US.

The company also has the expertise of George Garibaldi as chief medical officer, a former Roche vice-president.

Costa said: “The successful licensing of these exciting clinical-stage product-candidates from Roche, together with our up-sized CHF54 million Series A financing, will enable Noema to reach value-creating development milestones with all four products.”

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Eisai forges CNS alliance with UK’s Wren Therapeutics

Japanese drugmaker Eisai has teamed up with UK biotech Wren Therapeutics on an R&D programme seeking drugs for neurodegenerative disorders.

The two companies will focus their efforts on alpha-synuclein, a pathway that has been implicated in disorders such as dementia with Lewy bodies (DLB) and Parkinson’s disease (PD).

DLB and PD are both so-called synucleinopathies, diseases that are characterised by mutations in the SNCA gene coding for alpha-synuclein, leading to the production of misfolded, toxic forms of the protein that clump together and are thought to damage nerve cells.

Wren – a spinout from the universities of Cambridge in the UK and Lund in Sweden – has developed a drug discovery platform that can be used to screen small-molecule drugs to see if they can bind to misfolded proteins and correct their structure, preventing them from aggregating.

It’s a similar concept to interfering with the aggregation of beta-amyloid to form neurotoxic plaques in diseases like Alzheimer’s disease – another of Wren’s research targets.

Under the terms of the agreement, Cambridge-based Wren’s “network kinetics” platform will be deployed alongside Eisai’s drug discovery expertise in neurodegenerative disorders.

Eisai has a long heritage in this area, having been involved in the development of well-established Alzheimer’s drug Aricept (donepezil) and various other drugs for epilepsy, with a late-stage pipeline that includes Biogen-partnered anti-amyloid drug aducanumab, currently under review by the FDA.

“Synucleinopathies such as dementia with Lewy bodies and Parkinson’s disease represent a significant unmet medical need due to the lack of any effective disease-modifying treatments,” said Dr Teiji Kimura, who heads up drug discovery in Eisai’s neurology division.

“The accumulation of alpha-synuclein oligomers with protein misfolding is an important hallmark of these diseases,” he added.

Last summer, Wren raised 23 million in first-round financing to advance its internal R&D in the area of protein-misfolding diseases.

Other companies are also targeting alpha-synuclein, although Eisai and Wren are unusual in that they are seeking small-molecule candidates. Rivals include Roche and Prothera, which have an antibody in late-stage testing, as well as AstraZeneca/Takeda, Biogen, Lundbeck, AbbVie/BioArctic and Denali.

Roche licensed the antibody – called prasinezumab – from Prothera in a $600 million deal that dates back several years. Earlier this year however, the programme had a setback when a phase 2 trial in PD missed the mark.

The partners said the data showed some signs of efficacy, and prasinezumab is now heading for a phase 2b trial as an add-on therapy to standard levodopa therapy in PD.

Biogen has an antibody candidate called cinpanemab (BIIB054) in the phase 2 SPARK trial, due to generate results next year, while Lundbeck started a phase 1 trial in 2018 of Lu AF82422, another antibody, that could read out before year-end.

AZ and Takeda started a first phase 1 trial of their MEDI 1341 antibody in 2017, adding a second earlier this year that is due to run until 2022, while AbbVie’s ABBV-0805 cleared a phase 1 trial but seems to have been sidelined for strategic reasons.

Denali’s project is earlier in development. Its preclinical candidate ATV:aSyn is a bispecific antibody designed to penetrate the central nervous system more effectively, with one end targeting alpha-synuclein and another targeting a transporter in the blood-brain barrier.

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Biogen bulks up pipeline with Sage drugs in $3bn deal

With the prospects for its Alzheimer’s drug aducanumab still up in the air, Biogen has moved to shore up its late-stage pipeline with a $3 billion licensing deal with Sage that adds drugs for depression and neurological disorders.

The licensing agreement gives Biogen rights to Sage’s zuranolone (SAGE-217) for psychiatric disorders including depression, and SAGE-324 for essential tremor and other neurological diseases, which both target the GABAA receptor pathway.

In return Sage gets $1.525 billion upfront – $875 million in cash and a $650 million equity investment – as well as potential milestones of $1.6 billion if both drugs meet their development and commercial targets.

The deal comes as both companies are facing a challenging period. Biogen has invested heavily in its Alzheimer’s candidate aducanumab, but an FDA advisory committee was unimpressed with the company’s rehashed data for the anti-amyloid drug and voted that it didn’t support efficacy.

The FDA may still approve the drug – its reviewer had called some elements of the data persuasive in a briefing document – but even if it does getting payers to stump up for a drug with shaky data could be a challenge, despite the lack of Alzheimer’s therapies.

Meanwhile, Biogen has suffered recent setbacks including the failures of multiple sclerosis candidate opicinumab and a gene therapy for spinal muscular atrophy (SMA) – at a time when its big selling SMA drug Spinraza (nusinersen) is facing increased competitive pressure.

At the same time, Sage has struggled to make headway with its only approved therapy – Zulresso (brexanolone) for postpartum depression (PPD), which has been held back by a cumbersome dosing schedule that requires a 60-hour inpatient infusion.

Zulresso was launched last year but sales in the recent third quarter were just $1.6 million, around the same level as the same period of 2019.

With zuranolone, Biogen gets shared US and exclusive ex-US rights (excluding Japan, Taiwan and South Korea) to a potential first-in-class, once-daily oral drug with a breakthrough designation from the FDA as a treatment for major depressive disorder (MDD).

It has positive results from two pivotal trials – a phase 2 trial in MDD and phase 3 study in PPD – although a second phase 3 PPD trial (MOUNTAIN) failed to meet its primary objective. Biogen and Sage say there will be data readouts from other phase 3 trials in MDD and PPD next year.

The partners are going after three indications for the drug, namely PPD, as a rapid response therapy for MDD, and “as needed” treatment of acute MDD, and down the line will also look at its potential in bipolar disorder and generalised anxiety disorder.

A key characteristic is a rapid onset of action, which could free patients from the need to take antidepressants chronically and “may enhance quality of life and patient adherence”, according to Biogen.

SAGE-324 meanwhile is in phase 2 for essential tremor, a neurological disorder that causes involuntary and rhythmic shaking, and is being explored for other indications like epilepsy and Parkinson’s disease. Biogen gets shared US rights to the drug under the deal, as well as ex-US rights.

Essential tremor is estimated to affect over six million patients in the US, while 17 million Americans have symptoms of depression every year, and those numbers have led analysts to predict potential blockbuster sales for both zuranolone and SAGE-324 if approved.

Shares in Sage dipped after the announcement, with Jefferies analyst Andrew Tsai suggesting that might be because of disappointment that Sage hadn’t held out for potentially more favourable deal terms if zuranolone hits the mark in trials due to read out in 2021.

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FDA panel unimpressed with data for Alzheimer’s drug aducanumab

The FDA may have been minded to approve Biogen and Eisai’s Alzheimer’s candidate aducanumab, but its clinical advisors have little doubt that the evidence for the drug is lacking.

The much-anticipated advisory committee meeting held on Friday to discuss the marketing application for aducanumab proved to be a fractious affair, with both the companies’ data – and some of the FDA’s interpretation of it – under fire by panellists.

After hours of debate, the verdict from the experts was pretty unequivocal – 10 panellists voted against the main study supporting the drug, with just one saying they were uncertain about the data. Not one was convinced that the clinical trial results proved that the drug was effective.

The resounding rejection of the clinical data submitted in support of the marketing application for aducanumab came after the FDA published briefing documents that indicated the agency’s clinical reviewer was in favour of approval, calling the results “persuasive” despite a fairly damning assessment by the agency’s statistical expert in an appendix.

Aducanumab is vying to become the first Alzheimer’s drug designed to tackle an underlying cause of the disease, and the first new treatment for the neurodegenerative disease in almost two decades.

The FDA has been working closely with Biogen on the application and could still decide to approve the drug despite its experts’ reservations. That said, the balance of the votes makes that outcome unlikely – despite impassioned testimony during the virtual meeting by patient organizations.

The agency is due to make a decision by 7 March, and a review is also underway at the European Medicines Agency (EMA). Analysts have predicted it could become a multibillion-dollar blockbuster if approved, although at the moment that looks unlikely without another clinical trial.

An approval could also be seen as vindication for the hypothesis that tackling the amyloid plaques that are seen in the brains of people with the disease helps to slow the onset of symptoms. Many people had given up on the hypothesis after dozens of failed studies involving anti-amyloid drugs.

Biogen ran two identically-designed phase 3 studies of aducanumab – EMERGE (Study 302) and ENGAGE (Study 301) – to try to demonstrate that the anti-amyloid antibody could slow down the loss of cognitive function in people with mild cognitive impairment due to Alzheimer’s.

Last year, it called a halt to the studies after a futility analysis found it unlikely that aducanumab would show an effect on cognitive decline, but a few months later said that EMERGE was positive after all, and would form the basis of a marketing application with a phase 1b extension study – called PRIME – used as supportive evidence.

After a positive discussion of the results from Billy Dunn, acting director of the FDA’s office of neuroscience, the panel voted on three aspects of the data set.

In the first, they came down 8 to 1, with 2 uncertain, that the EMERGE trial could not be viewed on its own as providing strong evidence supporting aducanumab’s efficacy without taking into account the negative ENGAGE data.

They then voted 7 against and 4 uncertain on a question asking whether PRIME provide supportive evidence of the effectiveness of aducanumab in Alzheimer’s, before rejecting the premise that EMERGE could serve as primary evidence supporting the efficacy of the antibody.

Overall, the conclusion was that a negative interpretation of the data is just as likely as the positive one put forward by the trial sponsors, with one suggesting Biogen had shot first, and painted a bullseye later.

Biogen issued a short statement after the meeting in which CEO Michel Vounatsos said: “We appreciated the opportunity to share our data with the advisory committee, and we will continue to work with the FDA as it completes its review of our application.”

Trading in the biotech’s stock was halted ahead of the advisory committee meeting, but looks likely to be under considerable pressure when it resumes as it has been fluctuating wildly in reflection of the fortunes of aducanumab.

Biogen has a lot riding on aducanumab, as its pipeline has suffered recent setbacks including the failure of multiple sclerosis candidate opicinumab and a gene therapy for spinal muscular atrophy (SMA) at a time when big selling SMA drug Spinraza (nusinersen) is facing increased competition.

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China’s Green Valley prepares US trial of Alzheimer’s drug inspired by algae

As an influential panel of FDA-appointed experts prepares its verdict on Biogen’s Alzheimer’s drug, a little known China-based pharma is hoping to succeed where big name rivals have failed and develop a drug that is effective against the disease.

For almost two decades there has been no progress with new therapies for Alzheimers – the last new drug approved by the FDA was Forest’s Namenda (memantine) in 2003 and this only helps to relieve symptoms rather than tackling the root cause of the condition.

Since then the story of Alzheimer’s research has been one of expensive failures as experimental drugs, mainly targeting the amyloid plaques found in the brains of people with the disease, failed to stop or slow cognitive decline in clinical trials.

As Biogen hopes to change the narrative with aducanumab and a new analysis of a phase 3 trial initially written off as a failure, Shanghai Green Valley Pharmaceutical is beginning US trials of a radically different approach to treating the disease.

Green Valley’s drug known as GV-971 is a type of sugar extracted from brown algae and does not work directly on the brain at all: it tackles imbalances in the gut’s bacteria population that researchers believe may cause the brain inflammation leading to Alzheimer’s or Parkinson’s disease.

Last year China’s National Medical Products Administration (NMPA) became the first national regulator to approve the drug and the FDA gave the nod for US trials to begin earlier this year.

According to Bloomberg the first patient has been enrolled in a trial that the company hopes will show the cognitive improvements seen in the China-based trial that convinced the NMPA to approve GV-971.

The latest trial has been delayed because of the coronavirus pandemic but will enrol up to 2,046 people across China, the US and Europe, with the first 600 expected to sign up in the next six months.

Bloomberg noted that Green Valley needs the trials to win over sceptics who have questioned the authenticity of the data used by the NMPA for approval.

There is also confusion about why Green Valley has succeeded where the big western pharma companies have failed.

Whether Biogen gets the vote on Friday that could convince the FDA to approve aducanumab, or Green Valley succeeds with its trial, the prize for a drug that sets new standards in Alzheimer’s is huge.

A new Alzheimer’s drug would open up a market worth up to $30 billion in the US alone according to a Sanford C Bernstein & Co analysis cited by Bloomberg.

It’s unlikely that big pharma will be put off research, even if Biogen and Green Valley’s drugs are added to the ever-growing list of trial failures.

 

 

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Novartis’ Aimovig tops topiramate in migraine face-off

Novartis’ injectable migraine prevention antibody Aimovig has been shown to be more effective than topiramate – a go-to oral therapy for people with chronic migraine – in a head-to-head trial.

The HER-MES trial found that Aimovig (erenumab) was more effective at preventing migraine attacks and also better tolerated than topiramate, a generic epilepsy drug which is known to have side effects like sleepiness, dizziness, diarrhoea and nausea.

In the 777-patient study, fewer patients on Novartis’ drug discontinued treatment due to side effects, while more of them met the objective of a 50% reduction in the number of days in a month they had a migraine compared to high-dose topiramate.

Topiramate also needs to be taken twice a day, while Aimovig is given as an injection once a month and is available in a self-injector pen device. Both drugs can take up to three months for their effect on migraine prevention to fully kick in.

Novartis recorded Aimovig sales of $108 million in the first nine months of 2020, a rise of 44% on the same period of 2019, and says it is the most prescribed drug in the CGRP inhibitor class with 480,000 patients using it worldwide.

Quarterly sales have however fallen from a strong launch in 2018, and the drug can’t seem to generate the momentum needed to meet blockbuster sales expectations voiced during its development.

Part of that is the entry into the market of CGRP rivals, with three injectable drugs (Teva’s Ajovy and Eli Lilly’s Emgality) and one six-monthly infusion (Lundbeck’s Vyepti) now jostling for position in the migraine prevention market.

Meanwhile, two oral CGRP inhibitors – AbbVie’s Ubrelvy and BioHaven’s Nurtec – have been launched for the on-demand treatment of acute migraine attacks. These don’t compete with Aimovig and the other prevention therapies directly, but are raising the profile of the CGRP class among migraine sufferers and their doctors.

This year of course there have also been access issues caused by the coronavirus pandemic that have had a particularly big impact on neurology prescribing, as well as a continued challenge in persuading doctors to switch to the new class from older drugs like topiramate and AbbVie/Allergan’s Botox.

It’s estimated that CGRP drugs have only penetrated 15% of the migraine prevention market, and that’s why the HER-MES results are so important to Novartis.

“These results further emphasise its potential to provide significant relief from migraine with an infrequent dosing compared with the oral treatment,” said Estelle Vester-Blokland, the company’s global head of neuroscience medical affairs.

The company has exclusive rights to the sell Aimovig outside the US, where Amgen records sales, with the exception of Japan. Novartis and Amgen are however locked in a legal battle over marketing rights to the drug.

Photo by Carolina Heza on Unsplash

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Salvia’s migraine implant could be breakthrough, says FDA

An implantable neurostimulation migraine device from Salvia BioElectronics has gained Breakthrough Device Designation from the FDA.

Traditional neurostimulation systems are not designed to be compatible with the anatomy of the head, so Netherlands-based Salvia has developed flexible bioelectronic foils (pictured) that could be inserted below the skin in a minimally invasive procedure.

Breakthrough Device designation is reserved for potential products that could offer an improvement over existing therapies for a serious disease, in terms of safety and efficacy.

The designation allows Salvia to have more frequent interactions with FDA regulators when preparing filings, with the possibility of a faster review of trial data.

The decision from the FDA follows Salvia’s 26 million euro ($30 million) fundraiser in September to fund further development of the therapy.

Migraine is the first cause of disability in under 50s, affecting one out of seven people, predominantly women.

People with migraine experience episodes of throbbing, pulsating pain, sometimes accompanied by nausea, vomiting, and sensitivity to light, that can last anywhere from a few hours to a few days.

More than 5% of patients suffer from chronic migraine, where they experience migraines for an average of 22 days per month.

The Series A investment round was led by Panakès Partners, INKEF Capital and SHS Gesellschaft für Beteiligungsmanagement with participation from BOM Brabant Ventures, Thuja Capital and Dolby Family Ventures.

The total raised includes a 5m ($5.78 million) euro deferred risk-bearing Innovation Credit from the Netherlands Enterprise Agency (RVO, part of the Dutch ministry of Economic Affairs and Climate Policy).

A group of drugs known as calcitonin gene-related peptide (CGRP) inhibitors have recently been approved to prevent or reduce attacks.

However there has been limited progress to find new treatments for migraines for patients with chronic disease.

The most common treatments are antidepressants, beta blockers, anti-seizure medications, painkillers and even botulinum toxin.

 

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NICE changes its mind on Novartis’ progressive MS drug Mayzent

UK cost-effectiveness agency NICE has backed Novartis’ Mayzent for secondary progressive multiple sclerosis (SPMS), after turning it down earlier this year in draft guidance.

The change of heart means Mayzent (siponimod) becomes the first oral disease-modifying therapy to be recommended for NHS use in SPMS patients with active disease, defined as relapses or evidence of active inflammation of neurons on imaging.

Secondary progressive disease can occur after the relapsing/remitting stage of the disease, where patients experience fewer or no relapses but find their disability is increasing.

In June, NICE said it wasn’t able to support the use of Mayzent because there was limited clinical evidence for its benefits in SPMS, and it was not persuaded by the cost-effectiveness modelling submitted by Novartis.

Now, a consultation period and a new commercial agreement with Novartis to supply the drug at a discount on its £1,643.72 monthly list price means that around 38,000 people with SPMS across the UK could get access to the drug – which the MS Society charity says is “a huge step forward” for patients.

The NICE judgment for England and Wales follows a positive verdict from the Scottish Medicines Consortium (SMC) a few days ago. In Northern Ireland, the Department of Health reviews NICE guidance before deciding on use of a new drug.

Mayzent provides a treatment option to many people living with MS where once there was none, according to the MS Society, which said that people transitioning from relapsing/remitting MS to SPMS “have faced an immensely difficult challenge – being forced to go from having a range of treatments available to them, to severely limited choices.”

At the same time, for some people living with the secondary progressive form of the disease who are able to take beta interferons – currently given by injection – Mayzent provides a less intrusive choice, according to the charity.

Historically, the diagnosis of SPMS with active disease has often been delayed or avoided due to uncertainty around disease progression, as well as the lack of any effective treatment, says Novartis.

“We are working closely with the NHS to ensure eligible patients can start benefiting from siponimod as soon as possible,” said Chinmay Bhatt, managing director for Novartis Pharma UK, Ireland & Nordics.

Mayzent has the same mechanism of action as Novartis’ older drug Gilenya (fingolimod), which is approved for RRMS but not SPMS.

The drug was approved in Europe in January based on the 779-patient phase 3 EXPAND trial which showed that it significantly reduced the risk of disease progression, including physical disability and cognitive decline.

In a subgroup of Mayzent-treated patients with active disease, the data showed that the risk of three-month and six-month confirmed disability progression was significantly reduced, by 31% and 37% respectively, compared with placebo.

“By slowing down disability progression and improving cognition, siponimod has the potential to allow people to carry on working, remain independent and stay connected with family and friends,”  commented David Martin, chief executive of the MS Trust patient organisation.

“More broadly, we hope that the availability of this new treatment will lead to a greater focus on services for progressive MS which would benefit a much wider group of people,” he added.

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Axovant pushes on with Parkinson’s gene therapy, despite investor cynicism

Axovant has said it plans to continue developing its Parkinson’s Disease gene therapy after reporting supportive data from a small cohort of patients from a phase 2 trial.

However shares in Axovant were down sharply after the announcement because of market sentiment that the New York biotech had been selective with the data it had shared in its update.

The data came from a second cohort of just four patients in the phase 2 clinical trial SUNRISE-PD, although the improvement in symptoms was dramatic.

Chief R&D officer Gavin Corcoran said that the therapy known as AXO-Lenti-PD could transform treatment of patients with Parkinson’s through a one-time shot of gene therapy.

The company plans to begin EXPLORE-PD, a randomised, sham-controlled study next year, which will evaluate safety and tolerability at higher volumes of infusion.

Latest results showed that in two evaluable patients in the cohort, there was a 21-point mean improvement in a score measuring motor function during “off” periods, a 40% improvement from the baseline average score of 52 in these patients.

There was also evidence of dose response when compared with results at lower doses.

However the company said that COVID-19 and a patient refusal in the cohort at UK trial sites meant that two of the patients could not be scored at the six-month follow-up.

All four subjects were able to complete all other efficacy assessments at six months, including the patient-recorded symptom diaries.

Axovant is working with sites and investigators to ensure safe and ethical data collection at future time points through the pandemic in accordance with regulatory guidance.

It added that the gene therapy was generally well-tolerated in four patients receiving gene therapy, with no serious adverse events at six months after a single administration in the four subjects.

The subjects had an average age of 57 years and an average duration of Parkinson’s disease of 13 years, the company said.

In patients with PD specialised neurons in the brain producing the neurotransmitter dopamine die and the patient’s movements become erratic and uncontrolled, progressively declining over time.

Parkinson’s is not a true genetic disease, although certain genes have been linked to an increased likelihood of onset.

But Axovant is using a gene therapy approach to treat the disease – Axo-Lenti-PD works by turning other neurons in the brain into dopamine factories to replace those lost as the disease progresses.

The company hopes that by taking this approach it will solve the problem of “off” periods that occur with conventional therapies.

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Patient from the USA Underwent Spinal Discectomy Surgery in Turkey

Mr. James Evans suffered from serious back pain and he was taking pain injections to ease his pain. After the prolonged use of pain injections, they also stopped working. He consulted his Chiropractor in the USA he told him to get the spinal surgery done for his back pain.

Mr. James had a discussion with his family and decided to take the treatment outside the USA as he was not comfortable with the hospitals in the USA. He started looking online and came across MediGence. He contacted us and our case manager contacted him immediately. Our case manager told him to share all his medical reports, scans, and, x-rays.

MediGence helped him with multiple options from Turkey out of which Mr. Evans settled for LIV Hospital under the care of Assoc. Prof. Dr. Selahattin Özyürek. He is one of the best Orthopedics and Traumatology surgeon associated with LIV Hospital having experience of more than 20 years in the field of Orthopedics and Traumatology.

Mr. James arrived in Turkey on 20th Aug and was received by the hospital staff at the airport. On the very same day, he went straight to the hospital for his COVID-19 tests. The next day he came to the hospital for consultations and physical examination. After the consultations, the doctor advised him pre-op tests which were done on the very same day. The next day doctors counseled him and recommended the microdiscectomy surgery for his back pain and planned his admission for the surgery.

His surgery was successfully done and just a few hours after the surgery he was made to walk. After the surgery, he was required to stay in the hospital for 2 days and after discharge, follow-up visits were planned for him in the week to come to see that he is recovering well. He is still in Turkey to finish his follow-up visits and to enjoy Turkey further.

He was very impressed with the services provided by MediGence starting from the very beginning, helping him choose the right hospital, assisting him with the hotel options, responding to his queries, arranging his pick-up, managing his hospital appointments. He strongly recommends MediGence to his friends, family and, others who are looking to travel overseas for the surgery.

Team MediGence wishes him a very happy and healthy future.

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Mission successful for Novartis after FDA approves ofatumumab in MS

It’s mission accomplished for Novartis after the FDA approved ofatumumab for multiple sclerosis, completing a project where the former cancer drug has been repurposed.

The FDA approved ofatumumab under the brand name Kesimpta for people living with relapsing forms of multiple sclerosis.

Kesimpta will have a list price of around $83,000 a year, which the company argues will make it one of the lowest-cost branded options in a highly competitive market where drugs like Sanofi’s Aubagio and Roche’s Ocrevus have strong footholds.

Novartis is also talking up Kesimpta’s “favourable” safety profile and an injector pen that allows the drug to be administered each month at home.

The company hopes this will give it a competitive advantage over Roche’s Ocrevus (ocrelizumab), which is given as an infusion every six months in a hospital clinic after two starter doses two weeks apart.

Novartis also pointed to trial data showing better efficacy and similar safety profile when compared with Sanofi’s oral MS drug Aubagio (teriflunomide).

Ofatumumab was first approved by the FDA as a cancer drug in chronic lymphocytic leukaemia (CLL), under the brand name Arzerra, in 2014 when it was owned by GlaxoSmithKline.

But Novartis took control of ofatumumab in 2015 as part of an asset-swap deal, picking up rights to its other uses in autoimmune diseases such as MS, and has completed a research project lasting around 10 years to reimagine the drug as a treatment for MS.

Patients taking the drug for CLL in the US will be transitioned over to an access programme at no cost.

Novartis will pay co-developer Genmab a lump sum of $30 million as payment for lost royalties.

Kesimpta works by targeting B-cells, which are the underlying cause of both multiple sclerosis and several kinds of blood cancer including CLL.

Approval of Kesimpta is based on results from the phase 3 ASCLEPIOS I and II studies, in which it demonstrated superiority versus Aubagio in significantly reducing the annualised relapse rate, three-month confirmed disability progression, and the number of gadolinium-enhancing T1 and new or enlarging T2 lesions.

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Roche takes on Alexion as FDA approves satralizumab in NMOSD

The FDA has approved Roche’s satralizumab for the rare autoimmune disorder Neuromyelitis Optica Spectrum Disorder (NMOSD), under the brand name Enspryng.

Roche is taking on Alexion’s blockbuster Soliris (eculizumab), which was approved in NMOSD last year and in June Viela Bio, a spinoff from AstraZeneca, also won approval for another rival, Uplinza (inebilizumab).

The big Swiss pharma had been hoping for approval in patients regardless of whether they have anti-aquaporin-4 (AQP4) antibodies.

But so far Roche has not produced enough data in the broader patient group and the FDA has instead approved Enspryng in patients producing the AQP4 antibodies.

However Roche is claiming an advantage over Soliris with a more patient-friendly administration regimen: Enspryng can be self-administered by a patient or a caregiver every four weeks.

Patients taking Soliris have to visit a clinic to get an injection via a drip every week for five weeks, then every fortnight.

Uplinza offers another easier option as it is infused every six months after two starter doses two weeks apart.

Roche has yet to release any information on Enspryng’s price, but has plenty of room to manoeuvre given Soliris’ list price of around $500,000 per year.

Enspryng has a different mechanism of action from Soliris too: Roche’s drug inhibits the IL-6 receptor that is believed to play a key role in inflammation associated with NMOSD while Soliris targets the complement system.

It was designed by Chugai, part of the Roche group, using antibody technology allowing for longer circulation and subcutaneous dosing every four weeks.

NMOSD is a rare, lifelong and debilitating autoimmune disorder of the central nervous system, often misdiagnosed as multiple sclerosis, that primarily damages the optic nerve and spinal cord, causing blindness, muscle weakness and paralysis.

Roche said that NMOSD will be launched in two weeks.

This approval is supported by results from two randomised controlled phase 3 trials, the SAkuraStar and SAkuraSky studies.

In those studies Enspryng showed robust and sustained efficacy and a favourable safety profile in adults with AQP4 antibody positive NMOSD.

Results were sustained for 96 weeks, significantly reducing the risk of relapse compared with placebo as a monotherapy and when used concurrently with baseline immunosuppressant therapy (IST), which has commonly been used to manage NMOSD symptoms associated with relapses.

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Bayer adds menopause drug to pipeline with KaNDy acquisition

Bayer is to buy UK-based KaNDy Therapeutics in a deal worth more than $800 million, adding the biotech’s menopause drug to its women’s health pipeline.

Bayer will pay $425 million up front and potential milestone payments of up to $450 million until launch, followed by potential undisclosed “triple digit million” milestone payments once the drug is on the market.

The deal is expected to close next month, subject to customary conditions such as anti-trust approval.

At the beginning of this year, KaNDy completed a phase 2b trial of its first-in-class drug NT-814, showing activity against symptoms of the menopause such as hot flashes and night sweats.

A phase 3 trial is expected to begin in 2021 and the company says that the compound could generate peak sales of more than a billion euros globally.

If successful the company hope the drug will steal market share from hormone replacement therapies such as Pfizer’s Premarin, which has been on the market for decades and has several safety warnings, including endometrial cancer and heart disease.

Bayer is adding to its women’s health portfolio through strategic collaborations and acquisitions.

Earlier this year it announced the expansion of its partnership with Evotec with a new five-year collaboration, looking for several drugs to treat polycystic ovary syndrome.

Bayer’s exclusive license agreement with Daré Bioscience for the US market, signed in January 2020, is focused on its investigational, hormone-free, monthly vaginal contraceptive currently in clinical development for the prevention of pregnancy.

Based near GSK’s research base in Stevenage and headed by CEO Mary Kerr, KaNDy was spun out of NeRRe Therapeutics in 2017, itself a spin-off from GlaxoSmithKline following its decision to withdraw from neuroscience R&D in 2012.

By spinning off, KaNDy was able to focus on its lead drug NT-814, an oral first-in-class neurokinin (NK) 1,3 receptor antagonist which treats the postmenopausal vasomotor symptoms seen following the menopause, such as hot flashes and sleep disturbances.

The drug addresses vasomotor symptoms by modulating a group of oestrogen sensitive neurones in the hypothalamus in the brain called the KNDy neurons.

In menopausal women these become hyperactive due to the absence of oestrogen, disrupting body heat control mechanisms resulting in the debilitating symptoms.

Astellas in August last year announced it is beginning pivotal phase 3 clinical trials for fezolinetant, which could be considered a competitor although it only works against the NK3 receptor.

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Roche takes on pricey rivals as FDA approves SMA drug

Roche is hoping to undercut hugely expensive rivals after the FDA approved its oral spinal muscular atrophy (SMA) drug Evrysdi (risdiplam).

Evrysdi is the third treatment approved for SMA, an ultra-rare muscle wasting disease that can begin in early childhood, after Biogen’s Spinraza (nusinersen) and Novartis’ Zolgensma (onasemnogene abeparvovec).

But Spinraza costs $750,000 in the first year of treatment and about half that price annually from then on.

Zolgensma costs about $2.1m for a single shot of the gene therapy, making it the most expensive drug in the world by many people’s reckoning, although the manufacturer argues this is justified given the costs of treating the condition in later life.

Roche has decided to price Evrysdi according to its weight, costing up to $340,000 per year, with the cost being under $100,000 annually for some younger patients.

While this is not cheap by anybody’s reckoning, Roche hopes that the less intimidating price tag, plus the patient-friendly oral administration method will give it a competitive edge.

The FDA approved Evrysdi for the treatment of spinal muscular atrophy (SMA) in adults and children two months of age and older.

Roche noted that Evrysdi showed clinically-meaningful improvements in motor function across two clinical trials in people with varying ages and levels of disease severity, including Types 1, 2, and 3 SMA.

Infants achieved the ability to sit without support for at least five seconds, a key motor milestone not normally seen in the natural course of the disease.

Evrysdi also improved survival without permanent ventilation at 12 and 23 months, compared to natural history.

A liquid medicine, Evrysdi is administered daily at home by mouth or feeding tube.

Evrysdi is designed to treat SMA by increasing production of the survival of the motor neuron (SMN) protein. SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and movement.

Roche leads the clinical development of Evrysdi as part of a collaboration with the SMA Foundation and PTC Therapeutics.

Evrysdi will be available in the US within two weeks for direct delivery to patients’ homes through Accredo Health Group, an Express Scripts specialty pharmacy.

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Biogen signs $2.1 billion Parkinson’s disease deal with Denali

Biogen has bought a licence to co-develop and co-market potential Parkinson’s disease drugs with US biotech Denali, in a deal worth more than $2.1 billion.

Denali has been working on small-molecule compounds capable of crossing the blood-brain barrier and Biogen has bought a licence to co-develop and co-market compounds known as LRRK2 inhibitors in Parkinson’s disease.

Biogen and Denali will co-market the lead LRRK2 product in the US and China, and Biogen will commercialise in all other markets.

A molecule codenamed DNL151, currently in phase 1 development, has been selected to progress into late stage clinical studies that are expected to begin in 2021.

Mutations in the LRRK2 gene can cause Parkinson’s disease. LRRK2 regulates lysosomes, which play a vital role in cell function by breaking down excess or worn-out cell parts, and can also destroy invading viruses and bacteria.

Function of lysosomes is impaired in Parkinson’s disease and may contribute to the neurodegeneration that causes the symptoms of the disease.

Inhibition of LRRK2 activity may slow the progression of Parkinson’s disease in patients with and without known genetic risks based on restoration of lysosomal function.

As well as the LRRK2 drug Biogen will also receive an exclusive option to license two preclinical programmes from Denali’s drug transport platform, which aims to improve brain uptake of biotherapeutics.

Denali’s TV platform is a proprietary technology designed to effectively deliver large therapeutic molecules such as antibodies, enzymes, proteins and oligonucleotides across the blood-brain barrier after intravenous administration.

Biogen will have right of first negotiation on two additional transport vehicle (TV) enabled therapeutics, currently at a preclinical stage, should Denali decide to seek a partner.

Biogen will make an upfront payment to Denali of $560 million and make a $465 million equity investment in Denali from the purchase of 13.3 million newly issued shares of Denali common stock at approximately $34.94 per share, representing 11.2% of Denali’s outstanding stock.

Should the LRRK2 program achieve certain development and commercial milestones, Denali will be eligible to receive up to $1.125 billion in potential milestone payments.

People who have Parkinson’s disease experience numerous symptoms, including tremors, slow movement, muscle stiffness and impaired balance.

As these symptoms become progressively worse, patients have difficulty walking, talking or completing other simple tasks.

Parkinson’s disease is the second most common neurodegenerative disease and there are no approved therapies capable of slowing progression.

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Roche doubles down on tau for Alzheimer’s, licensing UCB drug for $120m

Roche already has one Alzheimer’s candidate in its pipeline targeting tau, but has added a second via a deal with Belgian drugmaker UCB worth up to $2 billion.

The Swiss pharma group is paying $120 million upfront for exclusive global rights to UCB0107, an anti-tau antibody that is in a phase 1 trial in another disease – progressive supranuclear palsy (PSP) – but hasn’t yet started clinical development in Alzheimer’s.

UCB is retaining rights to UCB0107 in PSP, and will fund development of the drug through proof-of-concept studies in Alzheimer’s. At that point, Roche can either follow through with the license or return rights.

The drug becomes a backup to Roche’s semorinemab (RG6100), which is licensed from AC Immune and has already started two phase 2 trials in Alzheimer’s patients. One in early-stage (prodromal) patients – called TAURIEL – is due to generate results this year, and a second in patients with moderate symptoms is due to readout in 2021.

Tau is a protein that is found in cells of the central nervous system and is involved in the assembly and stabilisation of neuronal microtubules – channels used to transport substances to different parts of the nerve cell.

In Alzheimer’s the protein goes haywire, forming tangles that have been linked to cell damage and neuronal death. Tau tangles are one of the characteristic hallmarks of Alzheimer’s visible in the brain, along with amyloid plaques.

Most of the efforts of the pharma industry on funding Alzheimer’s therapies has focused on amyloid, with almost universally negative results. Some candidates remain in development, including Roche’s own crenezumab and gantenerumab, which remain in development despite negative trials.

Biogen and Eisai have already filed for approval of their amyloid-targeting antibody aducanumab, and while some analysts see the evidence for the drug as somewhat shaky, it has a chance of becoming the first disease-modifying drug to be approved for the disease.

Dozens of amyloid drugs have failed at the clinical testing stage, and as a result some drugmakers have turned their attention to tau protein as another possible therapeutic target for Alzheimer’s.

Along with Roche and UCB, other companies are working on tau. Furthest ahead is TauRx, which has a tau aggregation inhibitor called LMTX in a phase 2/3 trial (LUCIDITY) with results due in 2021 or 2022, although that drug failed to show a benefit over placebo in a phase 3 trial reported in 2016.

AbbVie has ABBV-8E12 in mid-stage testing, as does Biogen with its BIIB092 plus two other recently licensed drugs from Ionis and Sangamo. Meanwhile, Eli Lilly, AC Immune, Johnson & Johnson, Merck & Co, Anavex and Axon Neurosciences have other anti-tau drugs in early-stage clinical testing.

Roche’s head of pharma partnering, James Sabry, said the deal with UCB will “help expand our efforts on tau.”

He added: “Our commitment remains strong on exploring multiple approaches with the hope that our research and development, including this collaboration with UCB, will lead to a disease-modifying medicine that could positively impact millions of people with Alzheimer’s disease.”

UCB meanwhile says it plans to start a phase 3 trial of UCB0107 in PSP in the second quarter of next year.

PSP is a rare and progressive neurodegenerative condition that can cause problems with balance, movement, vision, speech and swallowing that also features a build-up of toxic tau in the brain.

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Eli Lilly’s P-tau217 Blood Test Demonstrate High Accuracy in Diagnosis of Alzheimer’s Disease

Shots:

  • The study involved 1402 patients across 3 cohorts: a) 81 patients in Arizona (34 with AD and 47 without), b) 699 in Sweden (301 with no cognitive impairment, 178 with mild cognitive impairment, 121 with AD dementia and 99 with other neurodegenerative diseases) and c) 622 in Colombia (365 with E280A mutations and 257 noncarriers)
  • Results:  P-tau217 accurately identified AD from other neurodegenerative diseases in both 1&2 cohort while in 3rd cohort P-tau217 was elevated in mutation carriers’ blood for 20yrs.before anticipated symptom onset and was associated with memory performance, published in JAMA
  • P-tau217 is better than blood-based biomarkers or MRI but did not perform significantly better than cerebrospinal fluid- or PET-based tau biomarkers. Moreover, the test has the potential together with digital tools for checking memory performance like smartphone apps, to improve the diagnosis of AD

Click here to­ read full press release/ article | Ref: Eli Lilly | Image: PharmaShots




Roche and UCB Collaborate to Develop UCB0107 for Alzheimer’s Disease

Shots:

  • UCB to receive $120M and is eligible to receive $2B as cost reimbursement, development, and commercial milestones as well as royalties on sales of the therapies, if Roche proceeds the clinical development. Roche to get an exclusive license to develop and commercialize UCB0107 for AD
  • UCB to fund and perform a POC study in AD and, upon the availability of the results of that study while Roche has the right to progress with the development or return full rights back to UCB
  • UCB0107 is an IgG4 mAb targeting a central Tau epitope, being developed to block/reduce the spread of Tau pathology. UCB continues to develop UCB0107 in PSP, with anticipated initiation of P-III study in Q2’21

Click here ­to­ read full press release/ article | Ref: PRNewswire | Image: PharmaShots




FDA approves Jazz Pharmaceuticals’ narcolepsy therapy

The FDA has approved Jazz Pharmaceuticals’ sleep disorder drug Xywav, to treat daytime sleepiness in patients with narcolepsy, offering a regime with less sodium than standard therapy.

Xywav (calcium, magnesium, potassium, and sodium oxybates) is an oral solution that has been approved in patients aged seven or older with narcolepsy.

Narcolepsy is a neurological disorder that involves a decreased ability to regulate sleep-wake cycles.

There is no cure and symptoms often include periods of excessive daytime and brief involuntary sleep episodes.

Dublin-based Jazz said it plans to launch Xywav by the end of the year after it puts into place a safety plan required by the FDA, which has identified the drug’s potential for abuse and misuse in a boxed warning.

Xywav will therefore be only available as part of a Risk Evaluation and Mitigation Strategy (REMS) as the FDA is sensitive to products that could be addictive in the light of the opiate addiction epidemic in the US.

FDA approval of Xywav is based on a a global phase 3 double-blind, placebo-controlled, randomised-withdrawal, multicentre study that demonstrated the efficacy and safety of Xywav in the treatment of cataplexy and EDS in patients with narcolepsy.

In the study, which enrolled 201 patients, Xywav demonstrated highly statistically significant differences in the weekly number of cataplexy attacks compared to placebo.

There are several dosing options available for adults and children – prescribers can titrate Xywav into unequal doses taken over the course of the night.

When patients start Xywav after sodium oxybate, Xywav treatment is begun at the same dose and regimen as sodium oxybate (gram for gram) and titrated as needed based on efficacy and tolerability.

Xywav is formulated to have 92% less sodium than sodium oxybate, the current standard of care for the condition.

Unlike sodium oxybate, Xywav does not contain warnings about high sodium content.

Richard Bogan, associate clinical professor at the University of South Carolina School of Medicine and lead investigator of the phase 3 study, said: “Xywav makes it possible for patients to have a lower-sodium oxybate treatment option.

“This may help patients taking sodium oxybate better align with daily sodium intake recommendations including those by the American Heart Association.

“The average American consumes too much sodium. Excess sodium intake has been linked with increases in blood pressure, hypertension, stroke and other cardiovascular disease.”

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Pandemic and currency headwinds hurt Roche in first half

Roche has announced half-year results showing the COVID-19 pandemic affected sales of its key products, with currency headwinds also weighing on revenues.

The Swiss pharma’s figures came shortly after its arch-rival Novartis conceded that it had hit similar problems as the pandemic meant fewer patients started new courses of its drugs.

Four of the company’s key drugs Hemlibra for haemophilia, Ocrevus for multiple sclerosis, and breast cancer drugs Kadcyla and Perjeta were all below analysts’ expectations.

However there was a better than expected performance from the company’s anti-inflammatory drug Actemra, which has been used in trials to counter some of the symptoms of COVID-19.

Group sales were just shy of 29.3 billion Swiss francs ($26.8 billion), which according to an analysis by Jeffries equity research was below analysts’ consensus of around 30.2 billion Swiss francs ($32 billion).

The company’s pharma division brought in sales of 23.2 billion Swiss francs ($24.6 billion), below a consensus prediction of around 24 billion Swiss francs ($25.5 billion).

Aside from the impact of the pandemic, the figures were also affected by currency fluctuations – although group sales were increased by 1% in constant exchange rates, they declined 4% in Swiss francs as a result of its continued appreciation against most currencies.

Management is still targeting low-mid single digit growth for both sales and earnings per share for the year.

CEO Severin Schwan said that the company was maintaining its outlook for the year, after signs of a recovery in June.

He said: “Roche’s regular business was significantly impacted by the pandemic in the second quarter. But we now see clear signs of recovery. Furthermore, the uptake of our recently introduced medicines and diagnostic tests continues to be strong.”

Jefferies noted the strength of the company’s pipeline, which includes phase 3 trials for Huntington’s and Alzheimer’s drugs.

But Roche earlier this year ended development of its balovaptan for paediatric autism, a drug predicted to produce peak sales of around $3 billion if it had been approved.

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